Nucleophilic Substitution Reactions Video Lecture - Class 12

welcome to a brief introduction to
nucleophilic substitution reactions
during this discussion we will be
looking at the sn1 and sn2 reaction
mechanisms and what sort of factors will
influence a reaction to run by one of
these two mechanisms but before we do
that let's discuss the basic components
of any nucleophilic substitution
reaction so that we can define them and
then use those definitions in our
discussion first is the nucleophile a
nucleophile can be defined as an
electron rich species which easily
donates an electron pair to form a new
Bond heterogenic lee so nucleophiles are
characterized by dense regions of
negative charge and the presence of lone
pair electrons which are easily given up
to form a new bond so in this sense a
nucleophile acts like a Lewis base the
alter-ego to the nucleophile is an
electrophile and these would be defined
as electron deficient species which
easily accept electrons to form the new
chemical bond heterogenic lee so
electrophiles are going to be
characterized by regions of dense
positive charge and in some cases an
incomplete octet of electrons so
electrophiles are very willing to accept
acting as Lewis acids and finally
because we're talking about substitution
reactions we have to have a leaving
group as well that is to say that if we
add the nucleophile we have to lose the
leaving group otherwise it's not
technically defined as a substitution
reaction so a leaving group would be any
substituent on a molecule which easily
is removed by the withdrawal of its
bonding electrons to form a separate
stable species so leaving groups would
be characterized by any type of group
which will tolerate the acceptance of
these electrons and the formation of a
negative charge within that particular
group as it is departing from the rest
of the molecule so now that we've
defined these players in the game let's
take a look at the two major classes of
nucleophilic substitution reactions and
see how these
different components behave in each of
the two mechanisms let's begin now by
considering the sn1 reaction in the
depiction on this slide you'll notice
the nucleophile in green this is the
entity which will be donating electrons
to form the new bond the leaving group
is depicted in pink and the
electrophilic carbon would be the carbon
at the center of our t-butyl group in
this case it looks like a t-butyl halide
you'll also notice that I've labeled the
entire molecule which is going to be
attacked as the substrate this is
typically how we refer to the molecule
which will undergo nucleophilic attack
during the reaction so let's say that
we're dealing with a t-butyl halide here
the entire t-butyl halide would be the
substrate for my nucleophilic
substitution reaction as the sn1
reaction initiates the leaving group
departs from the substrate and in doing
so it creates a stable intermediate so
if we look at the energy diagram for
this reaction on the reaction coordinate
there's going to be a local minimum
which corresponds to the formation of a
stable intermediate carbo cation now
let's watch that take place you notice
that the leaving group has departed
leaving us for the t-butyl cation and
this t-butyl cation is a stable
intermediate it's not long however
before this stable intermediate is then
attacked by the nucleophile and in this
step of the reaction we reach the more
stable final product so the sn1 reaction
occurs in two different isolated steps
first departure of a leaving group to
form the intermediate carbo cation and
second the nucleophilic attack of that
carbo cation to form the final product
what's particularly interesting about an
sn1 reaction mechanism is that although
I have shown the nucleophile attacking
from the opposite side of the substrate
this is not necessarily going to have to
be this way if instead my leaving group
departs and the nucleophile then attacks
from the same side of the substrate
we have a different type of product
depending upon the stereochemistry of
the starting material now in the case of
a t-butyl halide this won't have any
consequence whatsoever on the product
but if we were starting with the chiral
product notice that at this point we
would have an inversion of symmetry
around about 1/2 or in fact exactly half
of the products formed therefore one of
the consequences of the sn1 reaction is
that there is a complete loss of
stereochemistry
so some factors that favor this
particular type of reaction would
include use of weak nucleophiles the
weaker and nucleophile is the less
likely it is to attack before the
departure of the leaving group forming
the stable intermediate more substituted
substrates favored this mechanism
because hyper conjugation from alkyl
groups will stabilize the carbo cation
intermediate better leaving groups on
the substrate also favored the sn1
reaction because the leaving group is
more likely to depart before
nucleophilic attack occurs as is the
definition of an sn1 reaction and
additionally the solvent choice will be
important but that's also going to
depend somewhat upon the identity of the
nucleophile substrate and leaving groups
and therefore it's difficult to
specifically say that a polar or
nonpolar that a polar protic or polar a
protic solvent would be best this is
going to depend upon the circumstances
of the reaction now let's move on to the
sn2 reaction mechanism in this case i've
changed just a few things about the
reaction that we have depicted the first
is i have altered the nucleophile to
make it a hydroxide ion this is a much
better nucleophile than for example a
halide ion which we may have been what
we depicted in the previous slide the
other important change is we switch from
a t-butyl halide to a methyl halide as
our substrate this is because in order
to proceed through the sn1 reaction a
methyl halide would have to form methyl
cation which is a very very unstable
intermediate so this particular
substrate is much more likely to hold on
to its leaving group until it is
attacked by the nucleophile so here
we've identified our nucleophile as the
hydroxide our electrophile as the carbon
on the methyl halide and our leaving
group as the halogen on the methyl
halide let's begin the sn2 reaction
mechanism and see how this proceeds and
notice that the nucleophile first
attacks and the leaving group has not
yet completely departed from the
substrate this means that we form a
single transition state rather than a
stable intermediate so the consequence
of this is that our reaction coordinate
diagram will not have a local minimum as
it goes through this mechanism instead
there is simply a single concerted
process which results in the change from
starting materials to products and where
we've currently frozen the reaction is
at the transition state of this process
where the bond between the nucleophile
and substrate has only partially formed
and the bond between the remainder of
the substrate and its leaving group has
only partially broken now let's finish
our reaction and see what happens as
this transition state falls down our
energy diagram we reach a point at which
the leaving group has completely
departed and the new nucleophile has
attached itself to the substrate what's
interesting about this mechanism is that
this can only occur through the backside
attack which is to say that the
nucleophile must attack from the
opposing side of the substrate as the
leaving group departs because of this
feature of the mechanism sn2 reactions
will always proceed with complete
inversion of stereochemistry and so a
chiral starting material should result
in a chiral product in an sn2 reaction
so factors that favor this particular
mechanism include the presence of a
strong nucleophile as in this case
hydroxide
which has a very local dense negative
charge and plenty of electron pairs
which it's willing to donate to form
bonds less substituted substrates also
favored sn2 recall that in this example
we switched from a t-butyl halide to a
methyl halide to demonstrate the sn2
this is because the formation of methyl
cation is highly unlikely due to its low
stability and therefore the leaving
group is more likely to remain attached
to the substrate until the nucleophilic
attack takes place
additionally poor leaving groups also
favored the sn2 reaction because the
less likely the leaving group is to
depart before nucleophilic attack the
more likely the sn2 mechanism is to take
place and finally just as in the sn1
example solvent choice can be very
important but will depend somewhat upon
specific factors around whichever
reaction it is that you're running so
always think about solvent choice but
always think so carefully in terms of
this specific nucleophile substrate and
leaving groups and not just well an sn2
will always run by a certain or better
in a certain type of solvent so now that
we have considered each of the two basic
nucleophilic substitution reaction
mechanisms individually let's compare
them side-by-side starting with the
mechanism the mechanism of an sn1
reaction is two steps it involves first
the departure of the leaving group
followed by the attack the nucleophile
whereas the sn2 reaction occurs in a
single concerted step in which the
nucleophile attacks and the leaving
group departs simultaneously from a
kinetics perspective the sn1 follows
first order kinetics therefore it's rate
law will be determined by only the
concentration of the substrate and the
nucleophile does not enter into this
equation whereas in the sn2 reaction
because the substrate and nucleophile
are all reacting in a single step
both of their concentrations are
considered
from a stereo chemistry perspective the
sn1 reaction is expected to proceed with
a Rasim ization of any chirality in the
starting materials whereas in the case
of the sn2 stereochemistry is inverted
as a consequence of backside attack as
far as conditions which favor these two
mechanisms from the perspective of the
nucleophile the presence of a weak
nucleophile will influence a reaction to
run by the sn1 mechanism this is because
the nucleophile is less likely to attack
before departure of the leaving group as
opposed to the sn2 mechanism in which a
strong nucleophile will favor this
particular mechanism because it is more
likely to attack before the departure of
the leaving group the identity of the
substrate will also influence the
mechanism highly substituted substrates
such as secondary tertiary or resonance
stabilized species in which the carbo
cation is highly stabilized will
influence them to run by the sn1 whereas
the sn2 will run much more efficiently
when less substituted species are used
such as methyls
or primary alkyl halides and finally the
identity of the leaving group in the
case of sn1 reactions a good leaving
group is favourable because it is more
likely to depart and become the more
stable leaving group species before the
attack of the nucleophile whereas in the
sn2 reaction a poor leaving group is
more desirable because this leaving
group is more likely to stay on the
substrate until the nucleophile attacks
initiating its departure so this is a
basic overview of the sn1 and sn2
reaction mechanisms